To compare the symptomatic improvement of nasal symptoms following septoplasty with partial inferior turbinectomy (groups A) versus septoplasty alone (groups B) and to assess the improvement of nasal symptoms in both surgical groups before and after surgery by NOSE scale. This Tertiary Hospital based study was carried out between August 2012 and April 2014. 60 cases with septal deviation and contralateral inferior turbinate hypertrophy. Nasal Obstruction Symptom Evaluation (NOSE) scale for evaluating nasal symptoms. Patients were alternatively divided into two surgical groups, group A. Septoplasty with partial inferior turbinectomy and group B septoplasty alone. Post-operative patient's symptoms evaluated by NOSE scale at 1, 3 and 6 months. Data analysed using tables, graph and percentage and test of significance like paired t test, Friedman test, Chi square test used. Post operative improvement following both group A septoplasty with partial inferior turbinectomy and group B in those undergoing septoplasty alone was highly significant (p < 0.001) at post-op 1, 3 and 6 months subjectively. When both groups were compared those undergoing partial inferior turbinectomy surgery with septoplasty had highly significant results (p < 0.001) for subjective assessment by NOSE scale. This study showed that hypertrophied turbinate need to be addressed in chronic cases of nasal obstruction with deviated nasal septum and contralateral turbinate hypertrophy. partial inferior turbinectomy should be done in addition to septoplasty, its highly effective modality for the treatment of nasal obstruction in patients with deviated nasal septum. NOSE score can be used as a subjective tool for symptomatic measurement of patients with nasal obstruction.
Epstein Barr Virus (EBV or Human herpesvirus 4) belongs to the genus Lymphocryptoviridae, the gamma 1 subtype of the Subfamily Gamma herpes viridae and is one of the most common viruses in humans. It is present in all populations, infecting more than 95% of all individuals within the first four decades of life. In developing countries, infections occur very early in life with no specific characteristics other than the general symptoms of acute viremia. In developed countries however, the infection is usually delayed until adolescence or early childhood years where it causes infectious mononucleosis, a benign self-limiting lymphoproliferative disorder. Though the infection with EBV is benign in the acute stages and latent in the chronic phase in the vast majority of people, the virus has been demonstrated to be involved in the development of many malignancies with the list of such malignancies progressively increasing. The first association was with the endemic Burkitt’s lymphoma. Subsequently, other lymphomas (subtypes of Hodgkin’s and non-hodgkin’s lymphomas) are also known to be associated with EBV infection. Epithelial malignancies such as lymphoepitheliomas of nasopharynx and stomach are included in the list of EBV associated tumors. Tumors arise as a result of genetic and epigenetic alterations produced by the virus, which transforms the normal cell into an immortalized proliferating cell. Since Burke et al first detected EBV in undifferentiated lymphoepithelioma like gastric cancer in 1990, many researches are undertaken to prove the same. EBV expresses latent membrane protein which can be detected immune histochemically. Our study is aimed at detecting the EBV expression in gastric carcinoma cells.
Based on preclinical and clinical study data, anti-programmed cell death protein 1 (PD-1) drugs Pembrolizumab (P), and Nivolumab (N) have been considered equivalent in terms of response efficacy. Both the antibodies have IgG4 backbone but vary considerably in terms of the PD-1 epitopes they bind to.. Given that there is almost no overlap between the PD-1 binding sites there is a definite possibility of nuanced drug-dependent differences in patient response to treatment. These differences would not be possible to discern unless the same patient with the same tumor microenvironment were evaluated with both drugs simultaneously. We attempted to address this question using the near native FarcastTM TruTumor histoculture platform. Fresh surgically resected Head and Neck squamous Cell Carcinoma (HNSCC) samples (n=8) along with matched blood were collected from consented patients. The tumor sample was processed to generate explants that were distributed into arms. These arms were treated in culture with P (32.9 µg/ml) or N (132 µg/ml) for 72 hours. The response was characterized using histopathology, cytokine release and flow cytometry. T-cell re-invigoration was assessed by evaluating Interferon gamma release while a decrease in tumor content and/or increase in cleaved Caspase expression was correlated with tumor cytotoxicity Pre-treatment cytokine levels across control and both treatment arms were equivalent (z-score <1.5) across all samples. Additionally, when treated with the same drugs in duplicate arms similar tumor cytotoxic response was observed in the replicate arms (n=1). These data established arm equivalence. Post treatment with N or P, 6 out of 8 samples exhibited a T-cells reinvigoration phenotype. Of the remaining 2 samples, one exhibited tumor cytotoxicity with both treatments while the other showed tumor cytotoxicity only on N treatment. We evaluated the 6 samples that exhibited T-cell re-invigoration response further to understand the subtle differences in response to either N or P. While the response trends were similar for both drugs, the rate of response, as evaluated by significant increase in cleaved caspase-3 or decrease in tumor content, seem to be different in 3 samples. These 3 samples responded better with P compared to N.In this study, we broadly observed equivalent response to both the drugs with some patient samples responding slightly better to one over the other. Further studies are required to tease out the molecular reasons for these nuanced differences in response to these two anti-PD1 treatments. The FarcastTM TruTumor platform provides the unique opportunity to make personalized choice of the drug treatment that might provide best response in a patient. Citation Format: Satish Sankaran, Biswajit Das, Kowshik Jaganathan, Gowri Shankar K, Jayaprakash C, Ganesh MS, Amritha Prabha, Vijay Pillai, Syamkumar V, Chandan Bhowal, Rajashekar M, Oliyarasi M, Ritu Malhotra, Govindraj K, Nandini Pal Basak. Simultaneous comparison of response to two different anti-PD1 drugs in the same patient using a human tumor histo-culture platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6632.
Cytotoxic T-cells (CTLs) in the Tumor immune Microenvironment (TiME) play an important role in mounting anti-tumor immune response. Immunotherapeutic (I/O) agents like checkpoint inhibitor aim to prevent anergy whilst T cell agonists co-stimulate CTLs to reinvigorate them and thus leading to tumor cytotoxicity. In this study we investigate the abundance and functionality of the intratumoral CTLs post stimulation, across different tumor indications, to understand the differential response across samples and indications to immune cell stimulation. These include Head and Neck Squamous cell carcinoma (HNSCC), Renal Cell Carcinoma (RCC), stomach adenocarcinoma (ca-Stomach) and Triple Negative Breast Cancer (TNBC). Using the Farcast࣪ TiME tumor histo-culture platform, that preserves both tumor and immune components in culture, we stimulated tumor explants with anti-CD3 (10ng/ml) + IL2 (100units/ml) for T-cell activation. Supernatants were collected pre-treatment and at 24-hour intervals for evaluation of cytokine release. At termination the explants were either fixed in formalin to generate paraffin blocks or dissociated into single cells for flowcytometry. 3-5 samples from each tumor indication were included in this study. Flowcytometry based immunophenotyping indicated presence of 48.6% ±5.4 live CD3+ T-cells and 20.6% ± 3.1 live CD3+CD8+ CTLs across all indications in the absence of any stimulation. HNSCC, RCC and ca-Stomach had similar proportion of CTLs, while TNBC had much lower proportions of T cell and CTLs. HNSCC and TNBC had a very low proportion of functional Granzyme-B+ CTLs (0.29%±0.08) whereas ca-Stomach and RCC had relatively higher proportion of these cells (6.9%±2.5). The proliferating Ki67+ CTLs sub-population was low across all indications (0.37%±0.2). Upon stimulation there was a significant increase (>2.5-fold, p<0.05) in the proliferating CTLs sub-population across all indications though the cytokine release pattern varied. HNSCC showed a consistent increase (7.4-fold) in functional CTLs in all samples accompanied by a significant increase in INFɣ, Granzyme B and Perforin secretion. RCC and TNBC showed minimal change in functional CTLs but showed a significant increase in secretion of these cytokines. In ca-Stomach there was an increase in INFɣ secretion, but not Granzyme B and Perforin. In summary, while CTLs were present in TiME, the proportions of activated and proliferating sub-populations differed across indications. The presence of active CTLs did not always translate to tumor cytotoxicity. This could be due to other pro-tumor cells and factors that offset the anti-tumor activity of T cells. The TiME platform thus provides a unique platform to study complex interactions between tumor and intratumoral immune cell populations that could be further probed to understand differential response in patients to immunotherapy mediated tumor cytotoxicity. Citation Format: Nandini P. Basak, Vasanth K, Kowshik Jaganathan, Gowri Shankar K, Manimaran A, Rajashekar M, MS Ganesh, Amritha Prabha, Prakash BV, C Jaya Prakash, Sindhu Govindan, Ritu Malhotra, Pradeep Kar, Oliyarasi M, Anirudh Suri, Rachita Rao, Satish Sankaran. Differential T cell response within the tumor microenvironment observed across different indications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1986.
Introduction: Primary testicular lymphoma is a rare extranodal lymphoma accounting for only 1-2% of all Non-Hodgkin's lymphomas. It is the most common neoplasm in patients above 60 years of age. Diffuse large B-cell lymphoma is the most common lymphoma worldwide. It accounts for approximately 30% of all lymphoid malignancies. Case report: We report the case of a 64-year-old male with bilateral diffuse large cell, non germinal centre like B-cell lymphoma of the testes. MRI showed bilateral epididymitis with right sided orchitis and minimal left sided hydrocoele. Right high inguinal orchidectomy was done to confirm the diagnosis. 6 cycles of RCHOP adjuvant chemotherapy was given. He was, however, unable to tolerate the intensive treatment and chemotherapy regimen and succumbed to its adverse effects, 2 months after completion of the 6th cycle. Discussion: Primary Testicular Lymphoma is extremely rare with unilateral presentation, making a bilateral testicular lymphoma even rarer. Orchidectomy is the primary choice of intervention to come to a diagnosis. Aggressive systemic therapy offers the only chance there is of remission, but rate of relapse are still quite high. Conclusion: As primary testicular lymphoma is a rare condition, there is a lack of clinical data to guide the treatment. However, with the aid of retrospective data evaluation, better prognosis may be obtained.
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